This proposal deals with the study of a thymus abnormality observed in our colony of hydronephrotic rats, which appears to be the result of a mutation arising in one of the breeders. Preliminary observations show that the gene may be inherited as an autosomal recessive trait. The abnormality consists of aplasia of the thymus of varying degree. In seven of ten affected animals, however, no thymus could be seen. This application requests funds to maintain and develop this colony of thymusless rats so as to perpetuate the mutation and make available an experimental model which is of considerable importance to immunologist and hematologists. The following studies will be performed in athymic rats: 1) Breeding studies will seek critical data on the mode of inheritance, penetrance, and expressivity of the gene as well as on the fetal and newborn mortality produced by the mutation, 2) routine hematologic studies with particular attention to the circulating lymphocyte number, 3) analysis of the immunocompetence by determining the level of humoral and cellular antibodies after immunization with antigens which reacts specifically with thymus derived cells and those which do not involve thymus cells. Cell mediated immunity will also be studied using ear allografts, and 4) histologic examination of the lymphopoietic tissue including sections treated with anti-thymus derived cell serum (antitheta serum) to determine the lymphopoietic territories devoid of thymus cells in athymic rats. The long-term goal is to develop, characterize, and make available a colony of rats with hereditary athymia for further immunologic studies and transplantation experiments.